Recurrent episodes of angioedema in a 12 year-old with a family history of hereditary angioedema and contradictory lab data

10/28/2013
I have an interesting case. This is a 12 y.o. white female with a history of recurrent episodes of sore throat and neck swelling associated with difficulty swallowing on and off for over one year. Last September 2012 started to developed sharp, stabbing twinges of abdominal pain about 5 days/week. Some pains will start in the upper region and travel down to her lower abdomen; location is not consistent. These episodes occur about 1-3 times a day, when they occur, and generally last about 5 min. She describes the pain as like a "vacuum cleaner sucks in my stomach then releases it". No relief with BM. She was admitted last October 2012 due to severe abdominal pain requiring cholecystectomy (Scan: decrease gallbladder emptying; Abdominal CT: normal).

Even after her cholecystectomy she has continued with the recurrent abdominal pain. She had an upper endoscopy was normal with 5 negative biopsies of the stomach and esophagus. Stool cultures for Salmonella, Shigella, and Campylobacter were negative, as were C.diff toxin, white cells, giardia and cryptosporidium antigen testing.

Interestingly, her family history is remarkable for Hereditary Angioedema on Dad and paternal GM. Recently she has started to developed episodes of hand and lip swelling. So far, unable to identify any triggers except with heavy exercise.

Initial work up last October 2012: C1esterase functional activity of greater than 100% obtained on 10/18/12 from an unknown laboratory, a C1esterase quantitative determination of 12 (11-26) and normal C1q level.

Last May 2, 2013 she was seen at our ER with swelling to tongue and uvula without any hives. Her lab work at the ER during the acute phase (before Berinert): C1 Inhibitor Function: 90 (Normal > 67), C4: 10 mg/dl (LOW; normal 14-40). Abdominal MRI: normal. She was given BERINERT (C1 Inhibitor Esterase) for the first time with resolution of symptoms. The diagnosis of HAE was made by clinical trial of C1INH and FH .Last June 2013 she was started on Tranexamic Acid.

Since July 2013, she has continued with her recurrent episodes (hand swelling and abdominal pain requiring multiple doses of Berinert even with prophylactic Tranexamic acid. She was started on Cinryze infusions last September 2013. She is still having breakthrough episodes.

Will appreciate your suggestions.

A:

Thank you for your inquiry.

I am forwarding your inquiry to Dr. Bruce Zuraw, who, as you know, is an international expert in hereditary angioedema. As soon as we receive his response we will forward it to you.

Thank you again for your inquiry.

Sincerely,
Phil Lieberman, M.D.

We received a response from Dr. Bruce Zuraw. Thank you again for your inquiry and we hope this response is helpful to you.

Sincerely,
Phil Lieberman, M.D.

Response from Dr. Bruce Zuraw:

I do not think that the abdominal symptoms sound very much like hereditary angioedema. They occur too frequently, are too evanescent, and normal MRI if done during an attack would seem to exclude the possibility of bowel wall edema. Lab data does not support a diagnosis of HAE. Therefore, at the current time this diagnosis is very problematic. The need for multiple doses of Berinert and the failure of prophylactic Cinryze are consistent with the correct diagnosis not being HAE.

If you want to resolve the ambiguity caused by the slightly low C4 level, then you need to measure the C1 inhibitor functional activity using the chromogenic assay available through National Jewish complement lab. Several things should be noted. First, it would be best to measure this at least 3 days or even more after any injection of a C1INH concentrate. Second, the test can be falsely abnormal if the blood sample is not processed carefully and rapidly after it is drawn.